Research profile

Introduction

Sperm are produced in the testis in the epithelium that lines the seminiferous tubules. This process is called spermatogenesis and can be subdivided into distinct phases. First, there is active proliferation of so-called spermatogonia. A series of divisions is carried out through which millions of cells are produced on a daily basis. The last division of the spermatogonia renders spermatocytes. Spermatocytes carry out the second phase of the spermatogenic process "meiosis". During meiosis homologous chromosomes pair and parental and maternal genes are recombined.Subsequently, spermatocytes carry out two divisions leading to the formation of haploid spermatids. During the third phase of spermatogenesis, spermatids develop from round cells into sperm, a process called spermiogenesis. The spermatogenic process is supported by somatic cells, called Sertoli cells, that produce a number of growth factors essential for normal germ cell development. In between the seminiferous tubules there are Leydig cells that produce testosterone which is essential for proper development of spermatocytes and spermatids.

Research lines

- The emphasis of our research has always been on spermatogonial multiplication and especially on the spermatogonial stem cells (SSCs). SSCs are at the basis of the multiplication process ensuring a life-long production of sperm. These cells are localized in a stem cell niche in which their maintenance is kept secure. Presently, we are developing a computer model for the behaviour of SSCs in- and outside of the niche. Understanding how the niche is regulated is important as depletion of SSCs will lead to sterility while too much self-renewal of SSCs will lead to the formation of a tumour. Knowledge of the regulatory mechanisms operating in the niche may give tools to help in particular cases of male infertility.

- In collaboration with a group at the Sapienza University in Rome, attempts are made to improve our understanding of spermatogenesis in humans. In particular spermatogonial multiplication in primates is quite different from that in other mammals. In addition, there are important differences between spermatogenesis in humans and most other primates. Using donor organ material, attempts are made to understand spermatogonial multiplication and stem cell renewal in humans. This line of research involves confocal microscopy on human testis samples after staining for various markers and studying BrdU incorporation patters.

- In collaboration with many groups, the testicular phenotype of a great variety of mutations is studied. The questions to be solved here are which cell types are affected and at which step spermatogenesis is arrested. Together these studies provide an inventory of genes that are essential at various steps in the spermatogenic process. Knowledge of the genes that crucial for complete spermatogenesis, will be helpful in understanding failure of spermatogenesis in specific cases of male infertility. To that end, testis biopsies of infertile patients are studied as well.

Results

About 300 articles in peer reviewed scientific journals ( Pubmed de Rooij ) and about 50 chapters in Proceedings and Books.

H-index in Google Scholar - 100

Recent Book Chapters / Reviews:  

D.G. de Rooij. 2015. The spermatogonial stem cell niche in mammals. In: Sertoli cell biology. Ed. M.D. Griswold. Elsevier Inc., Amsterdam. Chapter IV. pp. 99-121.

D.G. de Rooij. 2017. Organization of the Seminiferous Epithelium and the Cycle, and Morphometric Description of Spermatogonial Subtypes (Rodents and Primates). In: The Biology of Mammalian Spermatogonia. Eds. J.M. Oatley and M.D. Griswold. Springer, New York, NY. pp. 3-20.

D.G. de Rooij. 2017. The nature and dynamics of spermatogonial stem cells. Development 144, 3022-3030.

G. Hamer, D.G. de Rooij. 2018. Mutations causing specific arrests in the development of mouse primordial germ cells and gonocytes. Biology of Reproduction 99, 75–86.

T. Endo, M.M. Mikedis, P.K. Nicholls, D.C. Page, D.G. de Rooij. 2019. Retinoic acid and germ cell development in the ovary and testis. Biomolecules 9, 775.